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Titolo:
Thalidomide analogue CC-3052 reduces HIV+ neutrophil apoptosis in vitro
Autore:
Guckian, M; Dransfield, I; Hay, P; Dalgleish, AG;
Indirizzi:
Univ London St Georges Hosp, Sch Med, Div Oncol, London SW17 0RE, England Univ London St Georges Hosp London England SW17 0RE on SW17 0RE, England Univ Edinburgh, Sch Med, Rayne Lab, Edinburgh, Midlothian, Scotland Univ Edinburgh Edinburgh Midlothian Scotland burgh, Midlothian, Scotland Dept Genitourinary Med, London, England Dept Genitourinary Med London England enitourinary Med, London, England
Titolo Testata:
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
fascicolo: 3, volume: 121, anno: 2000,
pagine: 472 - 479
SICI:
0009-9104(200009)121:3<472:TACRHN>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; HUMAN-IMMUNODEFICIENCY-VIRUS; FC-GAMMA-RIII; FACTOR-ALPHA; TNF-ALPHA; IN-VITRO; INTERFERON-GAMMA; INHIBITORY ACTIVITY; RESPONSE ELEMENT; PROTEIN-KINASE;
Keywords:
thalidomide; neutrophils; HIV; apoptosis; cAMP;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Guckian, M Univ London St Georges Hosp, Sch Med, Div Oncol, POB 17717,Cranmer Terrace, London SW17 0RE, England Univ London St Georges Hosp POB 17717,Cranmer Terrace London England SW17 0RE
Citazione:
M. Guckian et al., "Thalidomide analogue CC-3052 reduces HIV+ neutrophil apoptosis in vitro", CLIN EXP IM, 121(3), 2000, pp. 472-479

Abstract

Thalidomide has significant immunomodulatory properties and has been used successfully in the treatment of oral ulcers and wasting in HIV patients. However, its use is limited by its poor bioavailability due to low solubility and short half life in solution, and teratogenic and neurotoxic side-effects. Recently, water-soluble analogues of thalidomide with significantly greater immunomodulatory activity and reduced side-effects have become available. We examined the effect of thalidomide and one analogue, CC-3052, on neutrophil apoptosis following culture for 20 h in vitro. Apoptosis was assessed by reduced CD16 expression and Annexin V binding using flow cytometry. Thalidomide or CC-3052 alone had no effect on neutrophil apoptosis when used at physiological levels. However, when used together with prostaglandin E-2 (10(-7) m), a potent adenylate cyclase activator, CC-3052 but not thalidomide (both 10(-5) m) reduced apoptosis in neutrophils from normal and HIVdonors. The reduced apoptosis could not be attributed to the ability of CC-3052 to reduce tumour necrosis factor-alpha (TNF-alpha) production, but may be due to its PDE4 inhibitor properties, as it increased [cAMP](i), and mimicked the effect of increasing [cAMP](i) using dibutryl cAMP, a membrane-permeable analogue of cAMP. The results suggest a role for thalidomide analogue CC-3052 in reducing persistent activation of the TNF-alpha system in HIV without markedly impairing neutrophil viability.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 14:46:15